Pontomedullary structures, particularly the raphe magnus and reticular magnocellularis, have been shown to contribute an inhibitory influence to dorsal horn neurons via the dorsolateral fasciculus. This caudal brainstem mechanism is thought to play a major role in modulating the ascending transmission of nociceptive information. Though raphe-spinal and reticulo-spinal efferents have been well characterized, the nature of afferent inputs to the medulla which activate, or otherwise influence such a descending analgesic mechanism are poorly understood. Thus, to ascertain the afferent neurocircuitry which may be related to raphe-spinal and reticulo-spinal inhibitory mechanisms, we propose to use electrophysiological methods, combined with horseradish peroxidase labeling to: 1. describe afferent influences on raphe and adjacent magnocellularis neurons - somatosensory, mesencephalic, reticular, and spinal afferents of raphe nuclei and adjacent nucleus magnocellularis will be examined to determine the nature of their input, especially in regard to threshold latencies, summation, convergence, and interactions; 2. physiologically characterize raphe-spinal and non-spinal raphe neurons - neurons identified as raphe-spinal on the basis of antidromic activation from spinal cord, will be compared to non-spinal raphe neurons with respect to afferent input, physiological response, and location within the caudal raphe complex; 3. relate physiological responses of raphe-spinal, non-spinal raphe, and reticular neurons with their morphology, axon trajectory, and cytoarchitecture as revealed by HRP labeling - the various characterizations addressed in these studies will be used to provide a comprehensive classification of medullary neurons, particularly in terms of the cytoarchitecture of caudal medullary structures; 4. relate raphe physiology and cytoarchitecture with putative neuro-transmitter systems - an attempt will be made to determine whether the afferent responses and morphological characteristics of raphe-spinal projections can be dissociated on the basis of putative neurotransmitter systems. Immunocytochemistry methods will be used to stain for serotonin and substance P in intracellularly recorded raphe and magnocellularis cells labeled with HRP. These data may offer new insight into transmitter mechanisms responsible for the descending inhibitory action of medullary neurons.